Incidence of hydromorphone-induced neuroexcitation in hospice patients

J Palliat Med. 2013 Oct;16(10):1205-9. doi: 10.1089/jpm.2012.0467. Epub 2013 Aug 9.


Background and objective: To date, there are no known published studies that prospectively followed hospice patients receiving hydromorphone to evaluate the development of hydromorphone-induced neuroexcitation (HINE). The first objective of this study was to determine the incidence of HINE. The second objective was to identify factors influencing the presence or absence of HINE symptoms in hospice patients.

Methods: This was a noninterventional, prospective study. This study population included hospice patients 18 years of age or older who were admitted to one of two Nathan Adelson Hospice inpatient units in Las Vegas, Nevada, and were initiated on a scheduled regimen of hydromorphone. A total of 156 patients were enrolled and analyzed in this study. Data collection was performed by the study investigators using a standard data tracking form, including hospice diagnosis, gender, renal function, hydromorphone regimen, and whether or not the patient experienced neuroexcitatory symptoms. Data collection occurred from November 2010 to March 2011.

Results and conclusions: Based on the data collected in this study, it appears that the likelihood of HINE does increase with larger doses, increasing age, increasing serum creatinine, and the presence of malignant neoplasm. However, after adjusting for the variables in the logistic regression model, diagnosis of malignant neoplasm was not a significant predictor of HINE. Future studies may focus on evaluating metabolite levels, such as hydromorphone-3-glucuronide (H3G), in patients developing HINE symptoms. This may help to determine if the metabolites of opioids, such as H3G, are involved in the development of the neurotoxic symptoms.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Analgesics, Opioid / adverse effects*
  • Female
  • Glucuronates / adverse effects*
  • Hospice Care
  • Humans
  • Hydromorphone / adverse effects
  • Hydromorphone / analogs & derivatives*
  • Incidence
  • Kidney Function Tests
  • Male
  • Neurotoxicity Syndromes / epidemiology
  • Neurotoxicity Syndromes / etiology*
  • Nevada / epidemiology
  • Prospective Studies
  • Risk Factors


  • Analgesics, Opioid
  • Glucuronates
  • hydromorphone-3-glucuronide
  • Hydromorphone